Genetic anticipation, a phenomenon characterized by increased severity of symptoms and earlier age at onset of a disease in successive generations, is believed to be present in schizophrenia. In several neurodegenerative diseases showing anticipation, the mutation causing the disease is an expanded trinucleotide repeat. Therefore, genes containing trinucleotide repeats prone to expansion have become a suitable family of candidate genes in schizophrenia. A human calcium-activated potassium channel gene (hSKCa3), possibly mapping to chromosome 22q11–13, a region previously linked to schizophrenia, was recently described. This gene contains two contiguous expressed CAG repeat stretches. Recently, long allelic variants of one of these CAG repeats were found to be overrepresented in schizophrenic patients compared to normal controls. In this study we attempted to replicate this result and to study the relationship between the length of this CAG repeat on the one hand and the severity and age at onset of the disease on the other hand. No association with the disease or correlation with the severity of schizophrenia was identified. In addition, hSKCa3 was mapped to chromosome 1. Our results do not support the involvement of this particular CAG repeat-containing gene in schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:154–157, 1999. © 1999 Wiley-Liss, Inc.

REFERENCES

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215: 403–410.
10.1016/S0022-2836(05)80360-2
CAS PubMed Web of Science® Google Scholar
Bassett AS, Husted J. 1997. Anticipation or ascertainment bias in schizophrenia? Penrose's familial mental illness sample. Am J Hum Genet 60: 630–637.
CAS PubMed Web of Science® Google Scholar
Brais B, Bouchard JP, Jomphe M, Desjardins B, Dubé, M-P, Gosselin, F, Xie, Y, Tomé, F, Fardeau, M, Brunet, G, Samson, F, Mathieu, J, Prévost, C, Duranceau, A, Codère, F, Pericak-Vance, M, Bulman, D, Tapscott, SFT, Munsat, T, Feasby, T, Munsat, T, Pilarski, R, Morgan, K, Rouleau, GA. 1998. When genetics and history converge: The fine-mapping and North American introduction and diffusion of the French Canadian oculopharyngeal muscular dystrophy mutation. Am J Hum Genet In Press
Google Scholar
Brenner HD, Dencker SJ, Goldstein MJ, Hubbard JW, Keegan DL, Kruger G, Kulhanek F, Liberman RP, Malm U, Midha KK. 1990. Defining treatment refractoriness in schizophrenia. Schizophr Bull 16: 551–556.
10.1093/schbul/16.4.551
PubMed Web of Science® Google Scholar
Chandy KG, Fantino E, Kalman K, Gutman GA, Gatrgus JJ. 1997. Gene encoding neuronal calcium-activated potassium channel has polymorphic CAG repeats, a candidate role in excitotoxic neurodegeneration and maps to 22q11—q13, a candidate region for bipolar disease and schizophrenia disorder 4. Am J Hum Genet 61: 305 (abstract).
Google Scholar
Chandy KG, Fantino E, Wittekindt O, Kalman K, Tong L, Ho T, Gutman GA, Crocq M, Ganguli R, Nimgaonkar V, Morris-Rosendahl, DJ, Gargus, JJ. 1998. Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: A candidate for schizophrenia and bipolar disorders? Mol Psychiatry 3: 32–37.
10.1038/sj.mp.4000353
CAS PubMed Web of Science® Google Scholar
Faraone SV, Blehar M, Pepple J, Moldin SO, Norton J, Nurnberger JIX, Malaspina D, Kaufmann CA, Reich T, Cloninger CR, DePaulo JR, Berg KX, Gershon ES, Kirch DG, Tsuang MT. 1996. Diagnostic accuracy and confusability analyses: An application to the Diagnostic Interview for Genetic Studies. Psychol Med 26: 401–410.
10.1017/S0033291700034796
CAS PubMed Web of Science® Google Scholar
Gastier JM, Pulido JC, Sunden S, Brody T, Buetow KH, Murray JC, Weber JL, Hudson TJ, Sheffield VC, Duyk GM. 1995. Survey of trinucleotide repeats in the human genome: Assessment of their utility as genetic markers. Hum Mol Genet 4: 1829–1836.
10.1093/hmg/4.10.1829
CAS PubMed Web of Science® Google Scholar
Gorwood P, Leboyer M, Falissard B, Jay M, Rouillon F, Feingold J. 1996. Anticipation in schizophrenia: New light on a controversial problem. Am J Psychiatry 153: 1173–1177.
CAS PubMed Web of Science® Google Scholar
Karayiorgou M, Gogos JA. 1997. A turning point in schizophrenia genetics. Neuron 19: 967–979.
10.1016/S0896-6273(00)80390-6
CAS PubMed Web of Science® Google Scholar
Kendler KS, Diehl SR. 1993. The genetic of schizophrenia: A current, genetic-epidemiologic perspective. Schizophr Bull 19: 261–285.
10.1093/schbul/19.2.261
PubMed Web of Science® Google Scholar
Nurnberger, JI Jr, Blehar, MC, Kaufmann, CA, York-Cooler, C, Simpson, SG, Harkavy-Friedman, J, Severe, JB, Malaspina, D, Reich, T. 1994. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 51: 849–859, 863–864.
10.1001/archpsyc.1994.03950110009002
PubMed Web of Science® Google Scholar
O'Donovan, MC, Guy, C, Craddock, N, Bowen, T, McKeon, P, Macedo, A, Maier, W, Wildenauer, D, Aschauer, HN, Sorbi, S, Feldman, E, Mynett-Johnson, LX, Claffey, E, Nacmias, B, Valente, J, Dourado, A, Grassi, E, Lenzinger, EX, Heiden, AM, Moorhead, S, Harrison, D, Williams, J, McGuffin, P, Owen, MJ. 1996. Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder. Psychol Med 26: 1145–1153.
10.1017/S0033291700035868
PubMed Web of Science® Google Scholar
Paulson HL, Fischbeck KH. 1996. Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci 19: 79–107.
10.1146/annurev.ne.19.030196.000455
CAS PubMed Web of Science® Google Scholar
Petronis A, Bassett AS, Honer WG, Vincent JB, Tatuch Y, Sasaki TX, Ying DJ, Klempan TA, Kennedy JL. 1996. Search for unstable DNA in schizophrenia families with evidence for genetic anticipation. Am J Hum Genet 59: 905–911.
CAS PubMed Web of Science® Google Scholar
Philibert AR, Horelli-Kuitunen, N, Robb, AS, Lee, Y-H, Long, RT, Damschroder-Williams, P, Martin, BM, Brennan, M, Palotie, A, Ginns, EI. 1998. The characterization and sequence analysis of thirty CTG-repeat containing genomic cosmid clones. Eur J Hum Genet 6: 89–94.
10.1038/sj.ejhg.5200157
CAS PubMed Web of Science® Google Scholar
Reiss AL, Feinstein C, Toomey KE, Goldsmith B, Rosenbaum K, Caruso MA. 1986. Psychiatric disability associated with the fragile X chromosome. Am J Med Genet 23: 393–401.
10.1002/ajmg.1320230131
PubMed Web of Science® Google Scholar
Risch N. 1990. Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol 7: 3–16.
10.1002/gepi.1370070103
PubMed Web of Science® Google Scholar
Speight G, Guy C, Bowen T, Asherson P, McGuffin P, Craddock N, Owen MJ, O'Donovan, MC. 1997. Exclusion of CAG/CTG trinucleotide repeat loci which map to chromosome 4 in bipolar disorder and schizophrenia. Am J Med Genet 74: 204–206.
10.1002/(SICI)1096-8628(19970418)74:2<204::AID-AJMG19>3.0.CO;2-M
CAS PubMed Web of Science® Google Scholar
Tsuang MT, Faraone SV. 1995. The case for heterogeneity in the etiology of schizophrenia. Schizophr Res 17: 161–175.
10.1016/0920-9964(95)00057-S
CAS PubMed Web of Science® Google Scholar

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Volume88, Issue2

16 April 1999

Pages 154-157

Lack of association between the hSKCa3 channel gene CAG polymorphism and schizophrenia

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Lack of association between the hSKCa3 channel gene CAG polymorphism and schizophrenia

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